Thin, biocompatible coatings for medical devices and macroporous hydrogels for tissue engineering scaffolds are ideally formed from a water-soluble polymer such as poly(ethylene glycol) (PEG). One problem with pure PEG hydrogels as scaffolds, however, is that it can be difficult for cells to infiltrate and degrade them due to their density. Macroporous hydrogels, therefore, are desirable but require incorporation of a pore-forming substance (porogen), which may be difficult to control (e.g., a foaming agent) or remove (e.g., poly(methylmethacrylate) microbeads).
PEG microparticles can suitably be formed by: (1) copolymerizing PEG with a polymer that has a lower critical solution temperature (LCST) (e.g. precipitation polymerization) or (2) using a surfactant and/or mechanical agitation to form micelles or emulsions (emulsion polymerization). Above the LCST, a solvent for a polymer becomes a non-solvent, which can cause precipitation of the polymer. A frequently used LCST polymer is poly(N-isopropylacrylamide), which allows for the production of very small spherical microparticles from a solution that would otherwise form a bulk gel. The resulting small microparticles are relatively effective as coatings for medical devices, but exhibit far from perfect biocompatibility. A potential reason for the less than ideal biocompatibility may be the presence of a large proportion of hydrophobic poly(N-isopropylacrylamide). PEG microparticles may also be formed in emulsions, e.g. water in oil, PEG/dextran in water, or PEG surfactants above the cloud point (i.e., the temperature at which dissolved solids are no longer completely soluble, precipitating as a second phase giving the fluid a cloudy appearance). The presence of these additives/non-aqueous solvents/surfactants is generally not desirable because they may be difficult to remove from the formed articles. PEG/aqueous salt solutions can be phase separated at temperatures much less than 100° C. Upon mixing, however, the stability of the phases is known to be poor, which can lead to the formation of aggregates of microparticles, which has been known to be ascribed to the low viscosity of the solution. In some instances, the presence of a surfactant has been known to be necessary in order to prevent the formation of large aggregates.